Substance Concentration Monitoring Apparatuses and Methods

ABSTRACT

A substance concentration monitoring method includes inducing a periodic change in a body surface temperature over time using a heating and/or cooling element and yielding a function of temperature that varies with time so as to exhibit a temperature derivative with respect to time that oscillates periodically. Mid-infrared radiation absorbed or emitted from the body is measured while the surface of the body exhibits the oscillating, periodic derivative. The method includes determining a measured value based on the MIR radiation measurements and determining a concentration of a substance in the body based on a correlation with the measured value. A substance concentration monitoring apparatus includes a processor that initiates operations continuously monitoring whether the concentration or the measured value are within a tolerance. The operations further include generating a warning output when the concentration or the measured value is outside the tolerance.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority under 35 U.S.C. §119 toU.S. Provisional Patent Application No. 62/014,518, filed on Jun. 19,2014 and entitled “Continuous Noninvasive Glucometer” and to U.S.Provisional Patent Application No. 62/028,884, filed on Jul. 25, 2014and entitled “Continuous Noninvasive Glucometer,” the contents of eachof which are herein incorporated by reference in their entirety.

BACKGROUND

Spectroscopic techniques using infrared (“IR”) radiation are known inthe prior art and have been widely used for non-invasive measurement ofthe concentration of substances of interest in a body. One area ofparticular interest is the use of these techniques for the non-invasivemeasurement of the concentration of glucose and other constituents ofthe human bloodstream. Several patents and patent applications disclosemethods to non-invasively measure the concentration of a substance, suchas glucose, for example, in the bloodstream using infrared detectionsystems and methods.

U.S. patent application Ser. No. 12/883,063, filed Sep. 15, 2010 andentitled “Method for non-invasive analysis of a substance concentrationwithin a body,” describes methods of measuring a concentration of asubstance, such as glucose, in a body. The described methods includechanging the temperature of the surface of a body from a firsttemperature to a second temperature, then changing the temperature ofthe surface of the body from the second temperature back to the firsttemperature. The method includes measuring a first amount of infrared(“IR”) radiation absorbed or emitted from the surface of the body in afirst wavelength band and a second amount of IR radiation absorbed oremitted from the surface of the body in a second wavelength band atpredetermined time intervals. The measurements occur during the timeperiod that the temperature of the surface of the body changes from thesecond temperature back to the first temperature. A concentration of thesubstance may be determined based on the measurements. The contents ofU.S. patent application Ser. No. 12/883,063 are hereby incorporated byreference in their entirety.

SUMMARY

A substance concentration monitoring method includes inducing a periodicchange in a temperature (T) of a surface of a body over time (t) using aheating and/or cooling element according to a periodic signal receivedby the element and yielding a function of temperature (T) that varieswith time (t) so as to exhibit a temperature derivative with respect totime (dT/dt) that oscillates periodically. Mid-infrared (MIR) radiationabsorbed or emitted from the body is measured while the surface of thebody exhibits the oscillating, periodic dT/dt. The method includesdetermining a measured value based on the MIR radiation measurements anddetermining a concentration of a substance in the body based on acorrelation with the measured value.

A substance concentration monitoring apparatus includes a processor, aheating and/or cooling element, an infrared sensor, and a memoryaccessible to the processor. The memory stores instructions that, whenexecuted by the processor, cause the processor to initiate operationsincluding generating a periodic signal configured to control the heatingand/or cooling element and thereby to induce a periodic change in atemperature (T) of a surface of a body over time (t) and to yield afunction of temperature (T) that varies with time (t) so as to exhibit atemperature derivative with respect to time (dT/dt) that oscillatesperiodically. The instructions also include collecting data from theinfrared sensor while the surface of the body exhibits the oscillating,periodic dT/dt, the data resulting from a measurement of mid-infrared(MIR) radiation absorbed or emitted from the body within a firstwavelength band in which a substance has an effect on MIR emission orabsorption and a measurement of MIR reference radiation absorbed oremitted from the body within a second wavelength band in which thesubstance has no or negligible effect on MIR emission or absorption. Theinstructions further include determining a measured value based on theMIR radiation data and the MIR reference radiation data and determininga concentration of the substance in the body based on a correlation withthe measured value.

Another substance concentration monitoring apparatus includes aprocessor and a memory accessible to the processor. The memory storesinstructions that, when executed by the processor, cause the processorto initiate operations including generating a consecutive plurality ofdata parameters indicative of respective concentrations of a substancein a body based on a corresponding plurality of mid-infrared (MIR)measurement sets. Each MIR measurement set of the plurality of MIRmeasurement sets includes a MIR measurement of the surface of the bodywithin a first wavelength band in which the substance has an effect onMIR emission or absorption and a MIR measurement of the surface of thebody within a second wavelength band in which the substance has no ornegligible effect on MIR emission or absorption. The instructionsinclude continuously monitoring the concentrations of the substance inthe body by determining whether the concentrations or the consecutiveplurality of data parameters are within a tolerance. The instructionsfurther include generating a warning output when one or more of theconcentrations or one or more of the consecutive plurality of dataparameters is outside the tolerance.

Another substance concentration monitoring method includes attaching acontinuous monitoring apparatus to a body and generating a consecutiveplurality of data parameters indicative of respective concentrations ofa substance in a body based on a corresponding plurality of mid-infrared(MIR) measurement sets collected with the continuous monitoringapparatus fastened to the body. Each MIR measurement set of theplurality of MIR measurement sets includes a MIR measurement of thesurface of the body within a first wavelength band in which thesubstance has an effect on MIR emission or absorption and a MIRmeasurement of the surface of the body within a second wavelength bandin which the substance has no or negligible effect on MIR emission orabsorption. The method includes continuously monitoring theconcentrations of the substance in the body by determining whether theconcentrations or the consecutive plurality of data parameters arewithin a tolerance. The method further includes generating a warningoutput when one or more of the concentrations or one or more of theconsecutive plurality of data parameters is outside the tolerance.

A further substance concentration monitoring apparatus includes ahousing, at least one MIR detector attached to the housing, aring-shaped heating and/or cooling element attached to the housing, anda thermally conductive ring in thermal communication with thering-shaped heating and/or cooling element. The apparatus includes atransmission window structure attached to the housing such that a lineof sight of the MIR detector passes through the transmission windowstructure, a surface of the transmission window structure, and a surfaceof the thermally conductive ring being aligned along a same planeoutside the housing.

BRIEF DESCRIPTION OF THE DRAWINGS

Some embodiments are described below with reference to the followingaccompanying drawings.

Referring to FIG. 1, a block diagram of an embodiment of a wearablesystem for continuously monitoring a concentration of a substance in abody is depicted and generally designated 100.

Referring to FIG. 2, an embodiment of a system for continuouslymonitoring a concentration of a substance in a body is depicted andgenerally designated 200.

Referring to FIG. 3, an embodiment of a detection configuration isdepicted and generally designated 300.

Referring to FIG. 4, an embodiment of a heating and/or cooling windowassembly is depicted and generally designated 400.

Referring to FIG. 5, an embodiment of a system for continuouslymonitoring a concentration of a substance in a body is depicted andgenerally designated 500.

Referring to FIG. 6, an embodiment of another window assembly for thesystem of FIG. 5 is depicted and generally designated 600.

Referring to FIGS. 7A and 7B, an embodiment of periodic signals andcorresponding periodic temperature changes are depicted.

DETAILED DESCRIPTION

Disclosed herein are embodiments of systems and methods tonon-invasively monitor a concentration of a substance of interest withina body. The monitoring may occur continuously. As an example, theembodiments described herein may be used to continuously monitor aconcentration of glucose in a person's blood. Some of the embodimentsdescribed herein may be worn for periods of time that range from severalminutes to days. The infrared measurements may be taken in the midinfrared (MIR) range, where infrared spectra exhibit wavelengths ofabout 6 to about 15 micrometers (μm).

Referring to FIG. 1, a block diagram of an embodiment of a wearablesystem for continuously monitoring a concentration of a substance in abody is depicted and generally designated 100. The system 100 mayinclude a controller 110, a power source 122, a display device 124, awireless transmitter 126, a mid-infrared (MIR) detector assembly 130, aheating and/or cooling window assembly 150, and an attachment mechanism170. The MIR detector 130 may include a preassembled sensor and anoptical element (not shown). For example, the optical element mayinclude a lens, and may focus raw IR radiation on the sensor in order todetect the radiation. In other embodiments, the optical element may be awindow.

The controller may include a processor 112 and a memory 114. Theprocessor 112 may include any circuitry capable of receiving andprocessing data. For example, the processor 112 may include amicroprocessor, a microcontroller, a peripheral interface controller(PIC), a digital signal processor (DSP), another type of processingelement, or any combination thereof.

The memory 114 may include one or more registers, cache memory, randomaccess memory (RAM), read only memory (ROM), solid state memory,magnetic disc memory, another type of volatile or non-volatile memory,or any combination thereof.

One or both of the processor 112 and the memory 114 may be implementedusing circuit logic, an application specific integrated circuit (ASIC),a field programmable gate array (FPGA), another type of circuitimplementation platform, or any combination thereof.

The memory 114 may be accessible to the processor 112 to enable theprocessor 112 to retrieve data from the memory 114 and to store data atthe memory 114. To illustrate, the memory 114 may include a processorreadable medium that may store instructions that, when executed by theprocessor, cause the processor to perform operations as describedherein.

The power source 122 may provide power to the controller 110, thedisplay device 124, the wireless transmitter 126, the MIR detectorassembly 130, the heating and/or cooling window assembly 150, or to anysubset thereof. The power source 122 may be lightweight and portable toenable the system 100 to be worn on a body without restricting movementof the body. The power source 122 may further hold a charge for extendeddurations to enable long term portability. For example, the power source122 may be capable of powering the system 100 for one or more dayswithout being recharged. In an embodiment, the power source 122 includesa rechargeable lithium ion battery pack.

The display device 124 may include any device capable of outputtingvisual or audio signals to a user of the system 100. For example, thedisplay device may include a liquid crystal diode (LCD) screen, abuzzer, another type of visual or audio output device, or anycombination thereof. Although FIG. 1 depicts the system 100 as includingthe display device 124, in some embodiments, the system 100 may omit thedisplay device 124. As an example, in some embodiments, the system 100may rely on a wireless transmission to a remote device to generate useroutputs.

The wireless transmitter 126 may include any device capable oftransmitting information to a remote device. The remote device mayinclude a mobile telephone, a portable music player, a tablet computer,a laptop computer, another type of computing device, or combinationsthereof. In some embodiments, the wireless transmitter may communicatewith the remote device via a network. For example, the network mayinclude a point-to-point network, a cellular network, a local areanetwork, a wide area network, another type of digital network, orcombinations thereof. Although FIG. 1 depicts the system 100 asincluding the wireless transmitter 126, in some embodiments, the system100 may omit the wireless transmitter 126. As an example, in someembodiments, the system 100 may rely on the display device 124 togenerate user outputs instead of the wireless transmitter 126.

The MIR detector assembly 130 may include devices capable of detectingMIR emission and/or absorption within one or more wavelength bands. Forexample, the MIR detector assembly 130 may detect MIR emission and/orabsorption in a first wavelength band where a substance of interest,e.g., glucose, affects the MIR emission and/or absorption and may alsodetect MIR emission and/or absorption in a second wavelength band wherethe substance of interest has no or negligible effect on the MIRemission and/or absorption. The first wavelength band may be referred toas a peak wavelength band and the second wavelength band may be referredto as a reference wavelength band. For example, for glucose, the firstwavelength band may be about 9.3 μm to about 9.9 μm. For glucose, thesecond wavelength band may be about 10.5 μm to about 15 μm. The MIRdetector assembly 130 may be further configured to measure the MIRemission and/or absorption of one or more blackbody devices, asdescribed further herein. Embodiments of the MIR detector assembly 130are described further herein.

The heating and/or cooling window assembly 150 may include devices forheating and/or cooling. The heating and/or cooling window assembly 150may also include at least one surface that is transparent to MIRradiation to pass the MIR radiation from a body to the MIR detectorassembly 130. Passing the MIR radiation may occur at the same time thatheating and/or cooling is performed. An embodiment of the heating and/orcooling assembly 150 is further described herein.

The attachment mechanism 170 may include any mechanism capable ofattaching one or more components of the system 100 to a body. Forexample, the attachment mechanism may include a buckle, a hook and loopfastener, a snap, another type of attachment device, or combinationsthereof. When the attachment mechanism 170 attaches the system 100 tothe body, the system 100 may be configured to ensure contact between theheating and/or cooling window assembly 150 and the body. The attachmentmechanism 170 may enable the contact to remain for long durations so thesystem 100 may be worn on the body.

During operation, the system 100 may continue to be worn on a body foran extended duration of time. For example, the system 100 may be wornfor more than 30 minutes, more than one hour, more than 5 hours, or forone or more days. During the duration of time, the attachment mechanism170 may hold the heating and/or cooling window assembly 150 in contactwith the body.

The MIR detector assembly 130 may take or otherwise generate a pluralityof MIR measurement sets over the duration of time that the system 100 isworn on the body. The plurality of MIR measurements may be taken withoutremoving the wearable apparatus from the body. Each MIR measurement setmay include a first MIR measurement of the body at the peak wavelengthband, where a substance of interest has an effect on MIR emission and/orabsorption, and a second MIR measurement at a reference wavelength band,where the substance has no or negligible effect on MIR emission and/orabsorption. In some embodiments, each measurement set may furtherinclude a MIR measurement of one or more blackbody devices within one orboth of the wavelength bands.

The MIR measurement sets may be taken through the heating and/or coolingwindow assembly 150. For example, MIR radiation from the body may passthrough a portion of the heating and/or cooling window assembly to theMIR detector assembly 130 to be measured.

While the plurality of MIR measurement sets are being recorded, theheating and/or cooling window assembly may heat and or cool a surface ofthe body. In some embodiments, the heating and/or cooling windowassembly may change a temperature of the body according to a periodicsignal received from the controller 110. Each measurement set taken bythe system 100 may correspond to a respective period of the periodicsignal. Further, each measurement set may be taken during a portion ofthe periodic signal where the rate of change in temperature of theheating and/or cooling window assembly or of the surface the body isconstant. In some embodiments, a period of the periodic signal is about60 seconds. The periodic signal may be configured to produce a periodictemperature pattern that correspond to a square wave, a triangle wave, asinusoidal wave, or combinations thereof. Examples of the periodicsignal and a resulting periodic change in temperature are describedfurther with reference to FIGS. 7A and 7B.

Referring to FIGS. 7A and 7B, an embodiment of periodic signals andcorresponding periodic temperature changes are depicted. FIG. 7A depictsa square signal wave 810. When the square signal wave 810 is applied toa heating and/or cooling device, it may result in a sinusoidaltemperature wave 820 at the surface of the body. FIG. 7B depicts asignal wave 830. When the signal wave 830 is applied to a heating and/orcooling device, it may result in a triangular temperature wave 840 atthe surface of the body. Measurement sets, as described herein, mayadvantageously be taken during portions of the triangular temperaturefluctuation 840 that exhibit a substantially constant rate oftemperature change. For example, measurements may be taken when theslope of the triangular temperature fluctuation, such as dT/dt, isapproximately constant or, preferably, actually constant.

Referring to either of FIGS. 7A and 7B, a measurement may be takenduring a positive dT/dt (where the temperature has a positive slope overtime) and another measurement may be taken during a negative dT/dt(where the temperature has a negative slope over time) at the sametemperature T. The measurements may be used to isolate a part of themeasurement that is f(dT/dt), which corresponds to the glucoseemission/absorption band.

MIR radiation emitted from the human body has two major contributors tothe MIR signal measured in a band where glucose has peakemission/absorption. First is the normal black body emission which iscorrelated to the 4th power of temperature (T⁴). The second contributoris glucose spectral emission/absorption. In cases where the measuredvolume is approximately in thermal equilibrium, the glucoseemission/absorption will approach zero, due to the fact that in thermalequilibrium the number of molecules that emit photons will be close tothe number of molecules that emit/absorb photons.

In order to create a measurable signal of glucose emission/absorption,the body matrix is taken out of thermal equilibrium. Furthermore, thephotonic relaxation is much faster than any other phenomenon of heattransfer. So if we take the body matrix out of thermal equilibrium wecan expect a short signal from glucose that will disappear once thesystem returns to thermal equilibrium. In order to create a continuousmeasurable signal from glucose molecules, we have to create continuouschange of the body matrix temperature, so that thermal equilibrium isnot reached.

The mathematical representation of emission/absorption due to continuoustemperature change will be:

$M = {{{{B\; B_{R}} \pm {{f\left( \frac{T}{t} \right)}*{f(N)}}} \pm p} \pm k}$

where m is a measured signal, BB_(r) is a Black Body radiation, f(dT/dt)is a function of the temperature derivative over time, f(N) is afunction of the number of glucose molecules in the measured volume, k isa constant, and p is a perturbation, emission or absorption of othersubstances.

First, we can replace N with:

N=V*C′

where V is a measured volume that is a constant of the apparatus usedand C′ is the concentration of glucose in this volume (for example,corresponding to tissue at a particular test site of the body). Wedenote this concentration as C′ as to not be confused with theconcentration in the blood (C). We expect C′ and C to be highlycorrelated.

By replacing V with k1 and moving it outside the function we now have:

$M = {{{{B\; B_{R}} \pm {k\; 1*{f\left( \frac{T}{t} \right)}*{f\left( C^{\prime} \right)}}} \pm p} \pm k}$

Note that f(dT/dt) is normalized such that it will be between 0 and 1,which will represent the relative number of molecules that we take outof Boltzmann equilibrium (based on the Boltzmann equation). For example,the Boltzmann equation may describe the change of a macroscopic quantityin a thermodynamic system. Being removed from Boltzmann equilibrium mayalter the emission and/or absorption of the molecules and, as such, mayhave an impact on the macroscopic emission and/or absorption of thebody. These molecules will be the population that emits or absorbsphotons (depending on the stimulation) and will be a fraction of thetotal number of molecules (C′).

In an embodiment, the measured volume may be stimulated with heating andcooling. We can separate the heating portion from the cooling portion ofstimulation using the equation above to represent measured signal foreach portion.

As such we have:

${M\; 1} = {{B\; B_{R}} + {{{k\; 1*{f\left( \frac{T}{t} \right)}*{f\left( C^{\prime} \right)}} \pm p} \pm k}}$

when the volume is being cooled, and:

${M\; 2} = {{B\; B_{R}} - {{{k\; 1*{f\left( \frac{T}{t} \right)}*{f\left( C^{\prime} \right)}} \pm p} \pm k}}$

when the volume is being heated.

If we choose a point where the temperature is the same in both equationsthen the Black Body radiation in both equations is the same. Subtractingthese equations results in

${{M\; 1} - {M\; 2}} = {2\left( {{{k\; 1*{f\left( \frac{T}{t} \right)}*{f\left( C^{\prime} \right)}} \pm p} \pm k} \right)}$

The device also measures radiation in a reference band (whereemission/absorption is negligible for glucose). Using the equation aboveand a value of 0 for f(C′) (because no glucose signal is being emitted)we can subtract two reference measurements at the same temperature toobtain the following equation:

R1−R2=2(p+k)

Further, p1=p2 if all the other material in the measured volume thatemits radiation in both wave bands has a flat emission spectrum, whichmeans that the emission or absorption in both wavelengths will be thesame as long as dT/dt is kept constant, that is, as long as dT/dt hasthe same absolute value at the same temperature.

We can then use the combination of the two peak glucose measurements andthe combination of the reference glucose measurements to obtain thefollowing formula for a measured value (assuming we measure at the sametemperature and keep dT/dt constant across all measurements):

${\left( {{M\; 1} - {M\; 2}} \right) - \left( {{R\; 1} - {R\; 2}} \right)} = {2*k\; 1*{f\left( \frac{T}{t} \right)}*{f\left( C^{\prime} \right)}}$

where M2 and M1 are peak glucose band measurements, R2 and R1 arereference band measurements, k is a constant, f(dT/dt) is a factor forhow much the measured volume is stimulated, and f(C′) is a function forhow many glucose molecules are in the measured volume. In thecircumstance where f(dT/dt) is not constant or not sufficientlyconstant, then the formula may be divided by f(dT/dt) such that f(dT/dt)becomes the denominator in the measured value. As a result, dT/dt at thetime of MIR measurement may be included in the measured value.

The output of this function is correlated to the gold standard bloodglucose measurement where f(dT/dt) is a value between 0 and 1 and isselected to best fit the correlation with the test measurement. Forexample, C′ may be correlated to the actual concentration of thesubstance in the blood.

The controller 110 may generate a consecutive plurality of dataparameters indicative of respective concentrations of a substance in thebody based on the corresponding plurality of MIR measurement sets asdescribed herein. The plurality of data parameters may then be stored.For example, the plurality of data parameters may be stored at thememory 114, or at another memory of the system 100. In the context ofthe present document, “continuous” monitoring refers to measuringsubstance concentration over time while the monitoring apparatuscontinues to contact the body between consecutive measurements. That is,even though the monitoring apparatus may be programmed to take ameasurement at periodic intervals, any interval may be selected. Themonitoring apparatus is capable of taking a measurement at any timesince it is not removed from contact with the body between consecutivemeasurements. An operator may program a selected measurement interval.Also, the monitoring apparatus may automatically change measurementintervals, depending on programmed conditions. For example, morefrequent measurement may be warranted when concentration approaches alevel of concern.

As the system 100 is worn on a body, the concentration of the substancewithin the body may be continuously monitored by determining whether thesubstance concentrations or the consecutive plurality of data parametersare within a tolerance. For example, as new data parameters indicativeof the concentration of the substance are generated at the processor112, the new data parameters may be compared to one or more tolerances.Alternatively or additionally, the concentrations may be compared to oneor more tolerances. The tolerances may be stored at the memory 114 orelsewhere in the system 100. If the new data parameter or concentrationis outside the tolerance, such as less than a lower tolerance or greaterthan an upper tolerance, a warning output may be generated and sent tothe display device. Alternatively or in addition, the warning output maybe sent to the wireless transmitter.

The wireless transmitter may be configured to send the warning output toa remote device. The remote device may include a cellular telephone, atablet, a laptop, or another type of mobile computing device. Thewarning output may indicate to the remote device to display a warning.The warning output may further indicate to the mobile device to contactan emergency service.

Based on the plurality of data parameters, the processor 112 maycalculate a continuous correlation function. Thereafter, the processor112 may modify at least one of the plurality of data parameters based onthe continuous correlation function. For example, as the processor 112generates new data parameters indicative of a concentration of thesubstance in the body, the processor 112 may adjust or otherwise modifythe new data parameters based on the continuous correlation function.Alternatively, the processor 112 may adjust or modify individual raw MIRmeasurements as they are received from the MIR detector assembly 130 anduse the modified MIR measurements in generating new data parametersindicative of a concentration of the substance. The continuouscorrelation function may reduce noise and/or measurement variations inthe plurality of MIR measurement sets.

To illustrate, the continuous correlation function may correlate betweenthe measurement taken and a “gold standard” blood glucose measurementmade at the same time. The function parameters are calibrated for eachperson. The function may be a polynomial, such as:

y=a+bx+cx ² +dx ³ +ex ⁴

where y is glucose concentration and x is the MIR measurement.

The difference of MIR measurement or ratio of MIR measurement isnormalized. Results may be normalized against a blackbody withpredetermined specifications and corrected for ambient temperature. Theparameters of a-e are determined from a set of calibration measurements.

During continuous measurements, there may be many more measurements (N)and the noise in the correlation function that limits its accuracy maybe reduced by √N. In addition to the above reduction in noise andincrease in accuracy, some embodiments may make use of the parameter ofmaximum change rate of glucose concentration in human body, which is 4mg/dL/min. In some embodiments, measurements may be taken every 3seconds, which means that the maximum change between adjacentmeasurements of glucose may be less than 0.2 mg/dL.

Given the above, a substance concentration monitoring method includesinducing a periodic change in a temperature (T) of a surface of a bodyover time (t) using a heating and/or cooling element according to aperiodic signal received by the element and yielding a function oftemperature (T) that varies with time (t) so as to exhibit a temperaturederivative with respect to time (dT/dt) that oscillates periodically.Mid-infrared (MIR) radiation absorbed or emitted from the body ismeasured while the surface of the body exhibits the oscillating,periodic dT/dt. The method includes determining a measured value basedon the MIR radiation measurements and determining a concentration of asubstance in the body based on a correlation with the measured value.

By way of example, the measured value may also be based on theoscillating, periodic dT/dt. Further, the measured value may becorrelated with glucose concentration. Measuring IR radiation mayinclude measuring the MIR radiation at a temperature during a positivedT/dt (an upward sloping temperature change) and measuring the MIRradiation at the same temperature during a negative dT/dt (a downwardsloping temperature change).

The measurement of IR radiation may include measuring a first MIRradiation at a temperature during a positive dT/dt (an upward slopingtemperature change), the measuring occurring within a first wavelengthband in which the substance has an effect on MIR emission or absorption.The measurement of IR radiation may also include measuring a firstreference MIR radiation at the temperature during the positive dT/dt,the measuring occurring within a second wavelength band in which thesubstance has no or negligible effect on MIR emission or absorption. Themeasurement of IR radiation may further include measuring a second MIRradiation at the temperature during a negative dT/dt (a downward slopingtemperature change), the measuring occurring within the first wavelengthband. The measurement of IR radiation may still further includemeasuring a second reference IR radiation at the temperature during thenegative dT/dt, the measuring occurring within the second wavelengthband.

In more detail, determining the measured value may include the first andsecond MIR radiation measurements and the first and second reference MIRradiation measurements in an equation that yields the measured value.The method may further include generating a correlation of the measuredvalue with the substance concentration. For example, a correlation toinvasively measured blood concentrations. Also, dT/dt may be determinedat the time the MIR radiation is measured and dT/dt may be included inthe measured value that is correlated with the substance concentration.

As will be appreciated, the present method or a similar method, such asotherwise described herein, may be implemented with a substanceconcentration monitoring apparatus. The apparatus may include aprocessor, a heating and/or cooling element, an infrared sensor, and amemory accessible to the processor. The memory stores instructions that,when executed by the processor, cause the processor to initiateoperations including generating a periodic signal configured to controlthe heating and/or cooling element and thereby to induce a periodicchange in a temperature (T) of a surface of a body over time (t) and toyield a function of temperature (T) that varies with time (t) so as toexhibit a temperature derivative with respect to time (dT/dt) thatoscillates periodically. The instructions include collecting data fromthe infrared sensor while the surface of the body exhibits theoscillating, periodic dT/dt. The data results from a measurement ofmid-infrared (MIR) radiation absorbed or emitted from the body within afirst wavelength band in which a substance has an effect on MIR emissionor absorption and a measurement of MIR reference radiation absorbed oremitted from the body within a second wavelength band in which thesubstance has no or negligible effect on MIR emission or absorption. Theinstructions include determining a measured value based on the MIRradiation data and the MIR reference radiation data and determining aconcentration of the substance in the body based on a correlation withthe measured value.

By way of example, the processor operations may further includemonitoring the concentration of the substance in the body by determiningwhether the concentration or the measured value are within a toleranceand generating a warning output when the concentration or the measuredvalue is outside the tolerance. Also, the apparatus may further includea wireless transmitter and the processor operations may further includesending the warning output to a remote device via the wirelesstransmitter to display a warning. For example, the remote device mayinclude a mobile telephone and the warning output may indicate that theremote device is to contact an emergency service.

The measured value may be additionally based on the oscillating,periodic dT/dt. The measured value may be correlated with glucoseconcentration. Also, collecting the data from the infrared sensor mayinclude collecting the data at a temperature during a positive dT/dt (anupward sloping temperature change) and collecting the data at the sametemperature during a negative dT/dt (a downward sloping temperaturechange). Determining the measured value may involve including the MIRradiation data and the MIR reference radiation data collected duringboth the positive and the negative dT/dt in an equation that yields themeasured value.

The periodic signal may be configured to produce a constant rate ofchange in temperature (dT/dt) of the heating and/or cooling elementduring both the positive and the negative dT/dt. As a result, collectingthe data may further include determining dT/dt at the time the MIRradiation is measured and determining the measured value may furtherinvolve including dT/dt in the measured value that is correlated withthe substance concentration. The periodic signal may be configured toproduce a periodic temperature pattern of the heating and/or coolingelement that corresponds to a square wave, a triangle wave, a sinusoidalwave, or a combination thereof.

Referring to FIG. 2, an embodiment of a system for continuouslymonitoring a concentration of a substance in a body is depicted andgenerally designated 200. The system 200 includes one or more printedcircuit boards (PCBs) 210, a housing 220, a battery 222, a first MIRdetector 230, a second MIR detector 231, a dichroic beam splitter 234,and a heating and/or cooling window assembly 250. The system 200 maycorrespond to an apparatus for measuring the concentration of glucosewithin a body.

The housing 220 may hold the MIR detectors 230-231 and the dichroic beamsplitter 234 together in a detection configuration. As such, the housing220 may serve as an accurate mechanical reference for the positioning ofthe MIR detectors 230, 231 and the dichroic beam splitter 234. Thehousing 220 may further be made of a material that conducts heat inorder to serve as a heat sink to stabilize the temperatures of thecomponents of the system 200. For example, the housing 220 may be madeof aluminum or an aluminum alloy.

The first MIR detector 230 and/or the second MIR detector 231 mayinclude a preassembled sensor and an optical element (not shown). Forexample, the optical element may include a lens, and may focus raw IRradiation on the sensor in order to detect the radiation. In otherembodiments, the optical element may be a window.

The one or more PCBs 210 may include pre-amplifiers, microprocessors,transmitters, receivers, and any other electrical components toimplement a controller, e.g., the controller 110. The power source 222may include a rechargeable lithium ion type battery and may bepositioned near the edge of the system 200 to enable easy access forreplacement. The heating and/or cooling window assembly 250 maycorrespond to the heating and/or cooling window assembly 150 and isfurther described with reference to FIG. 4.

Referring to FIG. 3, an embodiment of a detection configuration isdepicted and generally designated 300. For example, FIG. 3 illustratesthe configuration of the first MIR detector 230, the second MIR detector231, and the dichroic beam splitter 234. The first MIR detector 230 andthe second MIR detector may include thermopile detectors to detect lightwithin the MIR spectrum.

As depicted in FIG. 3, the first MIR detector 230 may receive IRradiation through the dichroic beam splitter 234 from a measurement area280. The second MIR detector 231 may receive the same IR radiationthrough the dichroic beam splitter 234. Both the MIR detectors 230, 231have a combined field of view after the dichroic beam splitter 234. Forexample, both the MIR detectors 230, 231 receive radiation from the samemeasurement area 280.

The first MIR detector 230 may be configured to detect MIR radiation ina first wavelength band (e.g., a peak band). The second MIR detector 231may be configured to detect MIR radiation in a second wavelength band(e.g., a reference band).

Referring to FIG. 4, an embodiment of a heating and/or cooling windowassembly is depicted and generally designated 400. The assembly 400includes a transmission window structure 452, a thermally conductivering 454, and a heating and/or cooling element 456.

The heating and/or cooling element 456 may be ring-shaped and may beattached to the thermally conductive ring 454. In some embodiments, athermally conductive adhesive is used to attach the heating and/orcooling element 456 to the thermally conductive ring 454. Further, insome embodiments, the heating and/or cooling element 456 is a Peltierelement.

The thermally conductive ring 454 may be thicker than the heating and/orcooling element 456 so the internal radius of the thermally conductivering 454 may be smaller than the internal radius of the heating and/orcooling element 456. In some embodiments, the thermally conductive ring454 includes aluminum or an aluminum alloy.

The transmission window structure 452 may be attached to the inside ofthe thermally conductive ring 454. Additionally, the transmission windowstructure 452 may have an outer down step ring to enable a surface 408of the thermally conductive ring 454 to be aligned and maintainalignment with a surface 409 of the transmission window structure 452along a single plane outside the housing 220.

During operation, the surfaces 408, 409 may contact a surface of a body.In some embodiments, the transmission window structure is made of amaterial that is substantially transparent to light within the MIRrange. For example, the transmission window structure may includegermanium, silicon, or both.

The heating and/or cooling window assembly 400 may correspond to theassembly 250 and may, in some embodiments, be attached to the housing220. For example, the heating and/or cooling element 456, the thermallyconductive ring 454, or both may be attached to the housing 220. Whenattached to the housing, the transmission window structure 452 may bepositioned such that a line of sight of the MIR detectors 230, 231passes through the transmission window structure 452.

Referring to FIG. 5, an embodiment of a system for continuouslymonitoring a concentration of a substance in a body is depicted andgenerally designated 500. The system 500 may include a PCB assembly 510,a MIR detector 530, a filter wheel 532, a heating and/or cooling element556, a thermally conductive plate 554, and a transmission windowstructure 552.

The components of the system 500 may be attached, or otherwise held inplace, by a metal base 520. The metal base 520 may be made of athermally conductive material such as aluminum. Metal base plate 520 mayfurther be coupled to a housing 512 that may enclose inner components ofthe system 500. The components of the system 500 may be powered by abattery 522 held in place by a battery cover 524. In an embodiment, thebattery 522 is a rechargeable lithium ion rechargeable type battery.

The PCB assembly 510 may include pre-amplifiers, microprocessors,transmitters, receivers, and any other electrical components toimplement a controller, e.g., the controller 110. The MIR detector 530may be coupled to the PCB assembly and may be positioned above thefilter wheel 532. In some embodiments, the MIR detector 530 may includea thermopile sensor as well as a germanium or silicon lens.

The filter wheel 532 may include a plurality of cavities 534 definedtherein. The plurality of cavities 534 may hold a plurality of filters.For example, the plurality of cavities 534 may hold a first filter thatpasses light in a first wavelength band where a substance affects MIRemission or absorption while blocking light that is not within the firstwavelength band. The plurality of cavities 534 may further hold a secondfilter that passes light in a second wavelength band where the substancehas no or negligible effect on MIR emission or absorption while blockinglight that is not within the second wavelength band.

Additionally, in one or more embodiments, one or more of the pluralityof cavities may hold a blackbody device to be used as a reference tostabilize continuous measurements of the MIR detector 530. The filterswithin the filter wheel 532 may be configured such that a line of sightof the MIR detector 530 is selectively aligned with one of the filtersor the blackbody device as the filter wheel 532 rotates. Motor 514 maycontact a periphery of filter wheel 532 to rotate it.

The thermally conductive plate 554 may retain the transmission windowstructure 552. Together, the thermally conductive plate 554 and thetransmission window structure 552 may form a surface that may contact asurface of a body during operation of the system 500. To that end, anouter surface of the transmission window structure 552 may be alignedwith an outer surface of the thermally conductive plate 554 along asingle plane outside the housing 512.

The heating and/or cooling element 556 may have a ring shape and may becoupled to the thermally conductive plate 554. In some embodiments, thethermally conductive plate includes aluminum or an aluminum alloy. Theheating and/or cooling element 556 may include an aperture definedtherein for MIR light to pass through. A heatsink 557 may be coupled tothe heating and/or cooling element to control the temperature and toprovide a temperature differential. Further, although not depicted inFIG. 5, in some embodiments, the filter wheel 532 may include fan bladesto create an air flow in contact with the heatsink 557. In someembodiments, the heating and/or cooling element may be a Peltierelement.

As depicted in FIG. 5, the plurality of cavities 534 of the filter wheel530 may be have an arcuate shape (e.g., a curved or bow shape). Thearcuate shape may enable multiple measurements to be performed through aparticular filter or blackbody device held in each cavity of theplurality of cavities 534 before the cavity rotates out of the field ofview of the MIR detector 530.

During operation, the filter wheel 532 may rotate at about 20 rotationsper minute (RPMs). At this speed, between five and six measurements maybe taken through each filter held by the plurality of cavities 534.Further, during the measurements, the thermally conductive plate 552 maycool and/or warm the surface of the body at approximately 60 secondcycles and amplitude of approximately 1 degree Kelvin.

Referring to FIG. 6, an embodiment of another window assembly for thesystem of FIG. 5 is depicted and generally designated 600. In thisembodiment window 610 is directly attached to the Peltier element 620without a metal interface. 640 is a thermal insulating plastic case sothe heat transfer from the window to other substances, except the skin,is minimal. On the upper part of the Peltier, a heat sink 630 isattached for keeping the temperature of the Peltier's upper plate atroom ambient temperature. The heat sink may be made of aluminum orcopper.

It will be understood that the details of features described withrespect to individual embodiments may be used in like features of theother embodiments described herein as consistent and appropriate eventhough not expressly indicated in describing the other embodiments.

In compliance with the statute, the embodiments have been described inlanguage more or less specific as to structural and methodical features.It is to be understood, however, that the embodiments are not limited tothe specific features shown and described. The embodiments are,therefore, claimed in any of their forms or modifications within theproper scope of the appended claims appropriately interpreted inaccordance with the doctrine of equivalents.

TABLE OF REFERENCE NUMERALS FOR FIGURES

100 system 110 controller 112 processor 114 memory 122 power source 124display device 126 wireless transmitter 130 MIR detector assembly 150heating/cooling window assembly 170 attachment mechanism 200 system 210PCB 220 housing 222 battery 230 MIR detector 231 MIR detector 234 beamsplitter 250 heating/cooling assembly 280 measurement area 300configuration 400 window assembly 408 ring surface 409 window surface452 transmission window structure 454 thermally conductive ring 456heating/cooling element 500 system 510 PCB assembly 512 housing 514motor 520 metal base 522 battery 530 MIR detector 532 filter wheel 534cavities 552 transmission window structure 554 thermally conductiveplate 556 heating/cooling element 557 heatsink 600 window assembly 610window 620 Peltier element 630 heat sink 640 plastic case 810 signalwave 820 temperature wave 830 signal wave 840 temperature wave

What is claimed is:
 1. A substance concentration monitoring methodcomprising inducing a periodic change in a temperature (T) of a surfaceof a body over time (t) using a heating and/or cooling element accordingto a periodic signal received by the element and yielding a function oftemperature (T) that varies with time (t) so as to exhibit a temperaturederivative with respect to time (dT/dt) that oscillates periodically;measuring mid-infrared (MIR) radiation absorbed or emitted from the bodywhile the surface of the body exhibits the oscillating, periodic dT/dt;determining a measured value based on the MIR radiation measurements;and determining a concentration of a substance in the body based on acorrelation with the measured value.
 2. The method of claim 1, whereinthe measured value is also based on the oscillating, periodic dT/dt. 3.The method of claim 2, wherein the measured value is correlated withglucose concentration.
 4. The method of claim 1, wherein measuring IRradiation comprises: measuring the MIR radiation at a temperature duringa positive dT/dt (an upward sloping temperature change); and measuringthe MIR radiation at the same temperature during a negative dT/dt (adownward sloping temperature change).
 5. The method of claim 1, whereinmeasuring IR radiation comprises: measuring a first MIR radiation at atemperature during a positive dT/dt (an upward sloping temperaturechange), the measuring occurring within a first wavelength band in whichthe substance has an effect on MIR emission or absorption; measuring afirst reference MIR radiation at the temperature during the positivedT/dt, the measuring occurring within a second wavelength band in whichthe substance has no or negligible effect on MIR emission or absorption;measuring a second MIR radiation at the temperature during a negativedT/dt (a downward sloping temperature change), the measuring occurringwithin the first wavelength band; and measuring a second reference IRradiation at the temperature during the negative dT/dt, the measuringoccurring within the second wavelength band.
 6. The method of claim 5,wherein determining the measured value comprises including the first andsecond MIR radiation measurements and the first and second reference MIRradiation measurements in an equation that yields the measured value andthe method further comprises generating a correlation of the measuredvalue with the substance concentration.
 7. The method of claim 1,further comprising determining dT/dt at the time the MIR radiation ismeasured and including dT/dt in the measured value that is correlatedwith the substance concentration.
 8. A substance concentrationmonitoring apparatus comprising: a processor; a heating and/or coolingelement; an infrared sensor; and a memory accessible to the processor,the memory storing instructions that, when executed by the processor,cause the processor to initiate operations including: generating aperiodic signal configured to control the heating and/or cooling elementand thereby to induce a periodic change in a temperature (T) of asurface of a body over time (t) and to yield a function of temperature(T) that varies with time (t) so as to exhibit a temperature derivativewith respect to time (dT/dt) that oscillates periodically; collectingdata from the infrared sensor while the surface of the body exhibits theoscillating, periodic dT/dt, the data resulting from a measurement ofmid-infrared (MIR) radiation absorbed or emitted from the body within afirst wavelength band in which a substance has an effect on MIR emissionor absorption and a measurement of MIR reference radiation absorbed oremitted from the body within a second wavelength band in which thesubstance has no or negligible effect on MIR emission or absorption;determining a measured value based on the MIR radiation data and the MIRreference radiation data; and determining a concentration of thesubstance in the body based on a correlation with the measured value. 9.The apparatus of claim 8, wherein the processor operations furthercomprise: monitoring the concentration of the substance in the body bydetermining whether the concentration or the measured value are within atolerance; and generating a warning output when the concentration or themeasured value is outside the tolerance.
 10. The apparatus of claim 9,further comprising a wireless transmitter, wherein the processoroperations further include sending the warning output to a remote devicevia the wireless transmitter to display a warning.
 11. The apparatus ofclaim 10, wherein the remote device includes a mobile telephone and thewarning output indicates that the remote device is to contact anemergency service.
 12. The apparatus of claim 8, wherein the measuredvalue is also based on the oscillating, periodic dT/dt.
 13. Theapparatus of claim 12, wherein the measured value is correlated withglucose concentration.
 14. The apparatus of claim 8, wherein collectingthe data from the infrared sensor comprises: collecting the data at atemperature during a positive dT/dt (an upward sloping temperaturechange); and collecting the data at the same temperature during anegative dT/dt (a downward sloping temperature change).
 15. Theapparatus of claim 14, wherein determining the measured value comprisesincluding the MIR radiation data and the MIR reference radiation datacollected during both the positive and the negative dT/dt in an equationthat yields the measured value.
 16. The apparatus of claim 14, whereinthe periodic signal is configured to produce a constant rate of changein temperature (dT/dt) of the heating and/or cooling element during boththe positive and the negative dT/dt.
 17. The apparatus of claim 8,wherein collecting the data further comprises determining dT/dt at thetime the MIR radiation is measured and determining the measured valuefurther comprises including dT/dt in the measured value that iscorrelated with the substance concentration.
 18. The apparatus of claim8, wherein the periodic signal is configured to produce a periodictemperature pattern of the heating and/or cooling element thatcorresponds to a square wave, a triangle wave, a sinusoidal wave, or acombination thereof.
 19. A substance concentration monitoring apparatuscomprising: a processor; and a memory accessible to the processor, thememory storing instructions that, when executed by the processor, causethe processor to initiate operations including: generating a consecutiveplurality of data parameters indicative of respective concentrations ofa substance in a body based on a corresponding plurality of mid-infrared(MIR) measurement sets, each MIR measurement set of the plurality of MIRmeasurement sets including a MIR measurement of the surface of the bodywithin a first wavelength band in which the substance has an effect onMIR emission or absorption and a MIR measurement of the surface of thebody within a second wavelength band in which the substance has no ornegligible effect on MIR emission or absorption; continuously monitoringthe concentrations of the substance in the body by determining whetherthe concentrations or the consecutive plurality of data parameters arewithin a tolerance; and generating a warning output when one or more ofthe concentrations or one or more of the consecutive plurality of dataparameters is outside the tolerance.
 20. The apparatus of claim 19,further comprising a ring-shaped heating and/or cooling element, whereinthe operations further include changing a temperature at the ring-shapedheating and/or cooling element according to a periodic signal.
 21. Theapparatus of claim 20, wherein each MIR measurement set of the pluralityof MIR measurement sets corresponds to a respective period of theperiodic signal.
 22. The apparatus of claim 21, wherein a period of theperiodic signal is 60 seconds.
 23. The apparatus of claim 21, whereineach MIR measurement set of the plurality of MIR measurement sets istaken during a portion of the periodic signal configured to produce aconstant rate of change in temperature of the ring-shaped heating and/orcooling element.
 24. The apparatus of claim 21, wherein the periodicsignal is configured to produce a periodic temperature pattern of thering-shaped heating and/or cooling element that corresponds to a squarewave, a triangle wave, a sinusoidal wave, or a combination thereof. 25.The apparatus of claim 19, further comprising an attachment mechanismconfigured to attach to the body, wherein the operations includerecording the plurality of MIR measurement sets while the attachmentmechanism is attached to the body.
 26. The apparatus of claim 19,further comprising at least one MIR detector and a transmission windowstructure, wherein the MIR measurement of the surface of the body withinthe first wavelength band and the MIR measurement of the surface of thebody within the second wavelength band are detected at the MIR detectorvia the transmission window structure.
 27. The apparatus of claim 19,further comprising a wireless transmitter, wherein the operationsfurther include sending the warning output to a remote device via thewireless transmitter to display a warning.
 28. The apparatus of claim27, wherein the remote device includes a mobile telephone and thewarning output indicates that the remote device is to contact anemergency service.
 29. The apparatus of claim 19, wherein the operationsfurther comprise calculating a continuous correlation function based onthe plurality of data parameters and reducing noise and/or measurementvariations in the plurality of MIR measurement sets.
 30. A substanceconcentration monitoring method comprising: attaching a continuousmonitoring apparatus to a body; generating a consecutive plurality ofdata parameters indicative of respective concentrations of a substancein a body based on a corresponding plurality of mid-infrared (MIR)measurement sets collected with the continuous monitoring apparatusfastened to the body, each MIR measurement set of the plurality of MIRmeasurement sets including a MIR measurement of the surface of the bodywithin a first wavelength band in which the substance has an effect onMIR emission or absorption and a MIR measurement of the surface of thebody within a second wavelength band in which the substance has no ornegligible effect on MIR emission or absorption; continuously monitoringthe concentrations of the substance in the body by determining whetherthe concentrations or the consecutive plurality of data parameters arewithin a tolerance; and generating a warning output when one or more ofthe concentrations or one or more of the consecutive plurality of dataparameters is outside the tolerance.
 31. The method of claim 30, furthercomprising changing a temperature of the surface of the body accordingto a periodic pattern generated by a heating and/or cooling element. 32.The method of claim 31, wherein each MIR measurement set of theplurality of MIR measurement sets corresponds to a respective period ofthe periodic pattern.
 33. The method of claim 31, wherein each MIRmeasurement set of the plurality of MIR measurement sets is taken duringa portion of the periodic pattern that has a constant rate of change intemperature.
 34. The method of claim 30, wherein the plurality of MIRmeasurements are taken without removing the wearable apparatus from thebody.
 35. The method of claim 34, wherein the plurality of MIRmeasurements are taken over a time of greater than 1 hour.
 36. Themethod of claim 30, wherein each MIR measurement set of the plurality ofMIR measurement sets further includes a MIR measurement of a blackbodydevice within the first wavelength band and a MIR measurement of ablackbody device within the second wavelength band.
 37. A substanceconcentration monitoring apparatus comprising: a housing; at least oneMIR detector attached to the housing; a ring-shaped heating and/orcooling element attached to the housing; a thermally conductive ring inthermal communication with the ring-shaped heating and/or coolingelement; a transmission window structure attached to the housing suchthat a line of sight of the MIR detector passes through the transmissionwindow structure, a surface of the transmission window structure, and asurface of the thermally conductive ring being aligned along a sameplane outside the housing.
 38. The apparatus of claim 37, furthercomprising a rotatable filter wheel containing: a first filter thatpasses light in a first wavelength band; and a second filter that passeslight in a second wavelength band, a line of sight of the MIR detectorselectively passing through the first filter or the second filter as thefilter wheel rotates.
 39. The apparatus of claim 38, wherein the filterwheel is configured to rotate at about 20 rotations per minute and theMIR detector is configured to sample MIR emission or absorption at least5 times through each filter as the filter wheel rotates.
 40. Theapparatus of claim 37, wherein the transmission window structurecomprises germanium, silicon, or both.
 41. The apparatus of claim 37,further comprising an attachment device configured to attach themonitoring apparatus to a surface of a body, the transmission windowstructure and the thermally conductive ring being configured tosimultaneously contact the surface of the body when the monitoringapparatus is attached.